The x-ray crystal structure of dimeric (+)-bornyl diphosphate synthase, a metal-requiring monoterpene cyclase from Salvia officinalis , is reported at 2.0-Å resolution. Each monomer contains two α-helical domains: the C-terminal domain catalyzes the cyclization of geranyl diphosphate, orienting and stabilizing multiple reactive carbocation intermediates; the N-terminal domain has no clearly defined function, although its N terminus caps the active site in the C-terminal domain during catalysis. Structures of complexes with aza analogues of substrate and carbocation intermediates, as well as complexes with pyrophosphate and bornyl diphosphate, provide “snapshots” of the terpene cyclization cascade.
Curvature extrema provide significant information about the shape of an image contour, such as a silhouette, and are the basis for the Hoffman-Richards codon representation for shape. This representation based on curvature easily translates into a binary string that will describe the abstract shape of any smooth image curve. The computation of the basic shape primitives requires dealing with two ever-pervasive problems: contour noise and scale. We show how contour noise can be estimated given knowledge of the shape of the filter used to compute curvature from the edge list of the contour. To handle the scale problem, we use an adaptation of Witkin's scale space. Our algorithm differs from Witkin's by using a notion of parts to set criteria for significant structures.
Bispecific antibodies (Bispecifics) demonstrate exceptional clinical potential to address some of the most complex diseases. However, Bispecific production in a single cell often requires the correct pairing of multiple polypeptide chains for desired assembly. This is a considerable hurdle that hinders the development of many immunoglobulin G (IgG)-like bispecific formats. Our approach focuses on the rational engineering of charged residues to facilitate the chain pairing of distinct heavy chains (HC). Here, we deploy structure-guided protein design to engineer charge pair mutations (CPMs) placed in the CH3-CH3′ interface of the fragment crystallizable (Fc) region of an antibody (Ab) to correctly steer heavy chain pairing. When used in combination with our stable effector functionless 2 (SEFL2.2) technology, we observed high pairing efficiency without significant losses in expression yields. Furthermore, we investigate the relationship between CPMs and the sequence diversity in the parental antibodies, proposing a rational strategy to deploy these engineering technologies.
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTNovel Poly(3-alkylthiophene) and Poly(3- alkylthienyl ketone) Syntheses via OrganomercurialsMark D. McClain, Douglas A. Whittington, Deanna J. Mitchell, and M. David CurtisCite this: J. Am. Chem. Soc. 1995, 117, 13, 3887–3888Publication Date (Print):April 1, 1995Publication History Published online1 May 2002Published inissue 1 April 1995https://pubs.acs.org/doi/10.1021/ja00118a033https://doi.org/10.1021/ja00118a033research-articleACS PublicationsRequest reuse permissionsArticle Views238Altmetric-Citations29LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InRedditEmail Other access optionsGet e-AlertscloseSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts
